Overweight or Obesity Without DiabetesPhase 3RISE-1NCT07896265
Efficacy And Safety of Olatorepatide in Adults With Overweight or Obesity Without Diabetes
A Phase 3 study testing Olatorepatide in people with Overweight or Obesity Without Diabetes, run by Regeneron Pharmaceuticals.
Trial summary
This study will test olatorepatide (study drug) to determine whether it can help treat overweight or obesity. In this study we will test how safe and how well olatorepatide works compared to placebo in people who are overweight or obese but do not have diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Overweight or Obesity Without Diabetes
- What is being tested?
- Olatorepatide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,000 participants
- Where
- No sites listed yet
- Study dates
- 18 Nov 2026to 23 Jan 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has BMI ≥30.0 kg/m^2 at screening OR BMI ≥27.0 kg/m^2 at screening with at least 1 of the following weight-related comorbidities: Hypertension, Dyslipidemia, Prediabetes, established Obstructive Sleep Apnea (OSA), established Coronary Artery Disease (CAD), Heart failure, established cerebrovascular disease, as described in the protocol
- History of one or more self-reported unsuccessful dietary attempts to lose weight
Who cannot join
- Have previous or current diagnosis of diabetes, including Type 1 Diabetes (T1D) or Type 2 Diabetes (T2D) or screening HbA1c ≥6.5% as described in the protocol
- Change in body weight >5 kg within 90 days prior to randomization as described in the protocol
- Current use or previous treatment in 90 days prior to screening with GLP-1-RA, GLP-1/GIP RA, related molecule, or any other Nutrient-Stimulated Hormone (NuSH)-based therapy
- Current treatment or treatment in 90 days prior to screening associated with weight loss or weight gain or high risk of initiation of such a treatment during the study duration as described in the protocol
- Previous or planned bariatric surgery
- Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase 3, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Olatorepatide, a GLP-1/GIP Receptor Agonist, in Participants Living With Overweight or Obesity Without Diabetes (RISE-1)
This study will test olatorepatide (study drug) to determine whether it can help treat overweight or obesity.
In this study we will test how safe and how well olatorepatide works compared to placebo in people who are overweight or obese but do not have diabetes.
Read more
The study is looking at:
- How well the study drug works
- How the body and blood and urine biomarkers change after taking the study drug, which can help researchers understand why the study drug may work better in some people than in others
- What side effects the study drug might cause
- How much of the study drug is in the blood at different times
- If the body makes antibodies to the study drug this may cause the study drug to not work as well
- Conditions
- Overweight or Obesity Without Diabetes
- Being tested
- Olatorepatide, Placebo
- Keywords
- Body weight, Waist circumference, Glucagon-Like Peptide-1 (GLP-1), Glucagon-Like Peptide-1 Receptor Agonist (GLP-1-RA), Control appetite, Control blood sugar, Gastric Inhibitory Polypeptide (GIP)
- Medical subject headings
- Overweight, Body Weight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlatorepatideDrug
Also called HS-20094
Administered per the protocol
PlaceboDrug
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| Olatorepatide-Dose 1 | Experimental | Not described Receives: Drug: Olatorepatide |
| Olatorepatide-Dose 2 | Experimental | Not described Receives: Drug: Olatorepatide |
| Olatorepatide-Dose 3 | Experimental | Not described Receives: Drug: Olatorepatide |
| Placebo-Dose 1 | Placebo comparator | Not described Receives: Drug: Placebo |
| Placebo-Dose 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in body weight
Measured: From baseline to week 72
Secondary outcomes (27)
Change in body weight
Measured: From baseline to week 72
Occurrence of ≥5% reduction in body weight
Measured: From baseline to week 72
Occurrence of ≥10% reduction in body weight
Measured: From baseline to week 72
Occurrence of ≥15% reduction in body weight
Measured: From baseline to week 72
Occurrence of ≥20% reduction in body weight
Measured: From baseline to week 72
Change in waist circumference
Measured: From baseline to week 72
Change in Systolic Blood Pressure (SBP)
Measured: From baseline to week 72
Change in Diastolic Blood Pressure (DBP)
Measured: From baseline to week 72
Change in Hemoglobin A1C (HbA1c)
Measured: From baseline to week 72
Change in Fasting Plasma Glucose (FPG)
Measured: From baseline to week 72
Percent change in total cholesterol
Measured: From baseline to week 72
Percent change in Low-Density Lipoprotein Cholesterol (LDL-C)
Measured: From baseline to week 72
Percent change in High-Density Lipoprotein Cholesterol (HDL-C)
Measured: From baseline to week 72
Percent change in non-HDL-C
Measured: From baseline to week 72
Percent change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C)
Measured: From baseline to week 72
Percent change in triglycerides
Measured: From baseline to week 72
Percent change in Apolipoprotein B (ApoB)
Measured: From baseline to week 72
Percent change in high-sensitivity C-Reactive Protein (hs-CRP)
Measured: From baseline to week 72
Percent change in urine Albumin-Creatinine Ratio (uACR)
Measured: From baseline to week 72
Change in Impact of Weight on Quality of Life-Lite-Clinical Trials (IWQOL-Lite-CT) Physical Function score
The IWQOL-Lite-CT is a 20-item PRO measure designed to assess the impact of changes in weight on patients' physical and psychosocial functioning. The range of possible scores for the IWQOL-Lite-CT is 0 to 100. Higher values indicate better participant functioning.
Measured: From baseline to week 72
Change in IWQOL-Lite-CT Physical Composite score
The IWQOL-Lite-CT is a 20-item PRO measure designed to assess the impact of changes in weight on patients' physical and psychosocial functioning. The range of possible scores for the IWQOL-Lite-CT is 0 to 100. Higher values indicate better participant functioning.
Measured: From baseline to week 72
Change in IWQOL-Lite-CT Total score
The IWQOL-Lite-CT is a 20-item PRO measure designed to assess the impact of changes in weight on patients' physical and psychosocial functioning. The range of possible scores for the IWQOL-Lite-CT is 0 to 100. Higher values indicate better participant functioning.
Measured: From baseline to week 72
Concentrations of olatorepatide in plasma
Measured: Up to approximately 76 weeks
Occurrence of Anti-Drug Antibody (ADA) to olatorepatide
Measured: Up to approximately 72 weeks
Magnitude of ADA to olatorepatide
Measured: Up to approximately 72 weeks
Occurrence of Neutralizing Antibody (NAb) to olatorepatide
Measured: Up to approximately 72 weeks
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Measured: Up to approximately 76 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2026
- Study start18 Nov 2026 (estimated)
- Primary completion19 Dec 2028 (estimated)
- Study completion23 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Overweight or Obesity Without DiabetesStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07896265
- Sponsor's protocol ID
- HS-20094-OB-2570
- Other IDs
- 2025-524861-26-00, 2025
- Acronym
- RISE-1
- Status last verified
- Oct 2026
- First submitted
- 19 Oct 2026
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Olatorepatide, a GLP-1/GIP Receptor Agonist, in Participants Living With Overweight or Obesity Without Diabetes (RISE-1)
- ClinicalTrials.gov ID
- NCT07896265
- Acronym / sponsor ID
- RISE-1 / HS-20094-OB-2570
- Conditions
- Overweight or Obesity Without Diabetes
- Keywords
- Body weight, Waist circumference, Glucagon-Like Peptide-1 (GLP-1), Glucagon-Like Peptide-1 Receptor Agonist (GLP-1-RA), Control appetite, Control blood sugar, Gastric Inhibitory Polypeptide (GIP)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2026 (estimated)
- Primary completion
- 19 Dec 2028 (estimated)
- Study completion
- 23 Jan 2029 (estimated)
- First posted
- 26 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test olatorepatide (study drug) to determine whether it can help treat overweight or obesity.
In this study we will test how safe and how well olatorepatide works compared to placebo in people who are overweight or obese but do not have diabetes.
The study is looking at:
- How well the study drug works
- How the body and blood and urine biomarkers change after taking the study drug, which can help researchers understand why the study drug may work better in some people than in others
- What side effects the study drug might cause
- How much of the study drug is in the blood at different times
- If the body makes antibodies to the study drug this may cause the study drug to not work as well
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Olatorepatide-Dose 1 | Experimental | Drug: Olatorepatide |
| Olatorepatide-Dose 2 | Experimental | Drug: Olatorepatide |
| Olatorepatide-Dose 3 | Experimental | Drug: Olatorepatide |
| Placebo-Dose 1 | Placebo comparator | Drug: Placebo |
| Placebo-Dose 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Has BMI ≥30.0 kg/m^2 at screening OR BMI ≥27.0 kg/m^2 at screening with at least 1 of the following weight-related comorbidities: Hypertension, Dyslipidemia, Prediabetes, established Obstructive Sleep Apnea (OSA), established Coronary Artery Disease (CAD), Heart failure, established cerebrovascular disease, as described in the protocol
- History of one or more self-reported unsuccessful dietary attempts to lose weight
Key exclusion criteria (6 listed)
- Have previous or current diagnosis of diabetes, including Type 1 Diabetes (T1D) or Type 2 Diabetes (T2D) or screening HbA1c ≥6.5% as described in the protocol
- Change in body weight >5 kg within 90 days prior to randomization as described in the protocol
- Current use or previous treatment in 90 days prior to screening with GLP-1-RA, GLP-1/GIP RA, related molecule, or any other Nutrient-Stimulated Hormone (NuSH)-based therapy
- Current treatment or treatment in 90 days prior to screening associated with weight loss or weight gain or high risk of initiation of such a treatment during the study duration as described in the protocol
- Previous or planned bariatric surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlatorepatideAlso: HS-20094Administered per the protocol | Drug | Olatorepatide-Dose 1, Olatorepatide-Dose 2, Olatorepatide-Dose 3 |
| PlaceboAdministered per the protocol | Drug | Placebo-Dose 1, Placebo-Dose 2 |
Primary outcome
Percent change in body weight
Time frame: From baseline to week 72
27 secondary outcomes
Change in body weight
Time frame: From baseline to week 72
Occurrence of ≥5% reduction in body weight
Time frame: From baseline to week 72
Occurrence of ≥10% reduction in body weight
Time frame: From baseline to week 72
Occurrence of ≥15% reduction in body weight
Time frame: From baseline to week 72
Occurrence of ≥20% reduction in body weight
Time frame: From baseline to week 72
Change in waist circumference
Time frame: From baseline to week 72
Change in Systolic Blood Pressure (SBP)
Time frame: From baseline to week 72
Change in Diastolic Blood Pressure (DBP)
Time frame: From baseline to week 72
Change in Hemoglobin A1C (HbA1c)
Time frame: From baseline to week 72
Change in Fasting Plasma Glucose (FPG)
Time frame: From baseline to week 72
Percent change in total cholesterol
Time frame: From baseline to week 72
Percent change in Low-Density Lipoprotein Cholesterol (LDL-C)
Time frame: From baseline to week 72
Percent change in High-Density Lipoprotein Cholesterol (HDL-C)
Time frame: From baseline to week 72
Percent change in non-HDL-C
Time frame: From baseline to week 72
Percent change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C)
Time frame: From baseline to week 72
Percent change in triglycerides
Time frame: From baseline to week 72
Percent change in Apolipoprotein B (ApoB)
Time frame: From baseline to week 72
Percent change in high-sensitivity C-Reactive Protein (hs-CRP)
Time frame: From baseline to week 72
Percent change in urine Albumin-Creatinine Ratio (uACR)
Time frame: From baseline to week 72
Change in Impact of Weight on Quality of Life-Lite-Clinical Trials (IWQOL-Lite-CT) Physical Function score
Time frame: From baseline to week 72
Change in IWQOL-Lite-CT Physical Composite score
Time frame: From baseline to week 72
Change in IWQOL-Lite-CT Total score
Time frame: From baseline to week 72
Concentrations of olatorepatide in plasma
Time frame: Up to approximately 76 weeks
Occurrence of Anti-Drug Antibody (ADA) to olatorepatide
Time frame: Up to approximately 72 weeks
Magnitude of ADA to olatorepatide
Time frame: Up to approximately 72 weeks
Occurrence of Neutralizing Antibody (NAb) to olatorepatide
Time frame: Up to approximately 72 weeks
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 76 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Related trials for Overweight or Obesity Without Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 2
Study of Olatorepatide in Adult Participants Living With Overweight or Obesity Without Diabetes
Overweight or Obesity
RecruitingPhase 3
Maridebart Cafraglutide Versus Semaglutide in Participants With Type 2 Diabetes
Diabetes Mellitus, Type 2
Not yet recruitingPhase 2
A Study to Evaluate Efficacy and Safety of BGM1812 Injection in Overweight or Obese Participants Without Diabetes
Overweight or Obese Participants Without Diabetes
RecruitingPhase 3
A Study to Evaluate the Effects of Enicepatide in Participants With Obesity or Overweight, With or Without Type 2 Diabetes
Obesity, Overweight
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Clinical Trial Management study director
Regeneron Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olatorepatide in people with Overweight or Obesity Without Diabetes, run by Regeneron Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in body weight (time frame: From baseline to week 72). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.